Research at Memorial Sloan Kettering Cancer Center is focused on cancer diagnosis and enhancing responses of tumor to treatment with a goal of curing cancer. Animal studies of novel cancer therapeutics, while imperfect as a treatment model, have utility, both in studying therapeutic efficacy and toxicity. Because tumors are heterogenous, both between individuals and within a single tumor, non-invasive imaging studies are necessary to provide information about variation in response. We propose to use three imaging technologies, nuclear magnetic resonance (NMR), positron emission tomography (PET), and quantitative autoradiography (QAR) to study a diverse range of topics that relate to cancer treatment. The three imaging techniques chosen were based on the fact that they are closely related. PET and QAR studies are synergistic, since QAR can be used to screen and evaluate new compounds that may be potential radiopharmaceuticals for PET. QAR and NMR both can evaluate blood flow and vascular permeability. PET and NMR can be used to investigate tumor metabolism, and clinically are often used in a complementary manner. The range of projects studied include predicting tumor response to treatment, dosimetry for radioimmunotherapy, pharmacology, gene therapy, tumor metabolism, and evaluating responses to novel cytostatic agents. In particular, we have focused on novel treatments, such as gene therapy, new "designer" drugs that are undergoing early clinical trials but lack endpoints since they are cytostatic. An important component of this research effort is in the imaging development effort. NMR studies will focus on designing better radiofrequency probes, enhancing spectral resolution, quantitation and image processing. PET research focuses on modeling, particularly of radiolabeled monoclonal antibodies, image processing and spatial registration. Dr. Blasberg will extend his previous novel developments in QAR and use 4 isotopes to study 4 different physiologic or biochemical processes within a tumor concurrently. Leadership will come from the imaging scientists (Drs. Koutcher, Blasberg and Larson) and also from the molecular pharmacology group. Monthly meetings between these two groups are viewed as essential to decide which problems are important and appropriate to be addressed by imaging technology. A Technology Committee also evaluate new imaging technologies for consideration.